Small Cell Lung CancerRobert Miller MD

www.aboutcancer.com

Types of Lung CancerNon-small cell carcinoma (NSCC)

(87%)◦Adenocarcinoma (38%)◦Squamous cell (20%)◦Large cell (5%)

Small cell carcinoma (13%)

Small cell lung cancer is virtually always caused by smoking and as smoking has decreased the incidence of this cancer has declined

Percent of Lung Cancers that were Small Cell:

1978: 20-25%, 1986: 17%, 2002: 13%NCDB Data for 2000-2010 small cell was 15%

Since women have not cut back on smoking as much as men, the frequency of small cell in women has increased

Women accounted for 28% in 1973 and in 2002 it was 50%

0%

5%

10%

15%

20%

25%

30%

35%

40 50 60 70 80

11%

31%

33%

19%

5%

Age Distribution: NCDB 2000-2010 for Small Cell Lung Cancer

Small Cell Lung Cancer

• These are classified as a neuroendocrine cancer

• These are fast growing cancers and only 1/3 are still confined to the chest

• Most patients are treated with chemotherapy and radiation but a small number (2- 5%) with early stage I may benefit from surgical resection

• 95% of small cell cancers start in the lung but 5% arise from outside the lung (e.g. Nasopharynx, gastrointestinal or genitourinary sites

Biopsy - confirm the cancer and determine the type

Bronchoscopy CT directed biopsy

Pathology

• Cancer cells should stain positive for keratin, epithelial membrane antigen and TTF-1

• Since they are neuroendocrine they should also stain for: chromogranin A, neuron specific enolase, NCAM and synaptophysin

“special stains”

Lung Imaging Lung Imagin

g

Lymph Nodes and Lung Cancer

Lymph Nodes in the Lung

Reading a CT Scan

Cross Section Anatomy of the Chest

Nodes on cross section

CT Small Cell

Usually large mass in the mediastinal lymph nodes and may compress the superior vena cava

Stages of Lung Cancer

Stage I – small spot no nodesStage II – larger or nodes on the side of the lung (hilar or N1 nodes)

Stage III – very large tumor or lymph nodes in the middles of the chest (mediastinum or N2 nodes)

Stage IV – metastases to other organs

Stage from NCDB

Stage 1 Stage 2 Stage 3 Stage 40

10

20

30

40

50

60

NSCLSCL

Stages for Small Cell

Veterans Affairs Lung Study Group defined limited stage (LS disease) as that confined to the ipsilateral hemithorax which could be safely encompassed within a tolerable radiation field and extensive stage (ES disease) as disease beyond the ipsilateral hemithorax, including malignant pleural or pericardial effusion or hematogenous metastases.

Patients with contralateral hilar or supraclavicular lymph nodes were excluded from some studies of LS disease, even though modern RT techniques can allow for high-dose RT to be delivered in selected cases.

Small Cell Stages

•Limited Stage: confined to the chest and regional nodes (1/3)•Extensive Stage: distant metastases (2/3)

Small Cell Carcinoma of the Lung usually presents with a large central tumor (hilar/mediastinal lymph node mass

Symptoms of Small Cell

• Because of the large lymph node swelling in the chest the patient may have shortness of breath, trouble swallowing, hoarseness, facial swelling (superior vena cava syndrome)

• Many present with symptoms of spread or metastases: headaches (brain met) bone pain (bone mets) or eating problems (liver mets)

• Some present with neurologic or endocrine paraneoplastic syndrome (e.g. low sodium or elevated calcium)

PET scan showing a typical small cell cancer with a large mediastinal mass making it hard to even see the heart on the left side

Small Cell Lung Cancer

NCCN.org

NCCN.com

Treatment for Small Cell Lung Cancer

Limited Stage: consider surgery resection for early stage followed by chemotherapy +/- radiation, otherwise most patients get chemotherapy plus radiation

Extensive Stage: unless very weak consider chemotherapy +/- radiation

The role of surgery in the treatment of limited disease small cell lung cancer: time to reevaluate.J Thorac Oncol. 2008 Nov;3(11):1267-71.

We identified 59 patients who underwent complete resection with nodal dissection for SCLC.

overall survival at 1 year of 76%

and 5 years 52%

Only 2 to 5% are candidates for surgery

Various chemotherapy schemes have been evaluated for SCLC; however, Cisplatin and Etoposide is widely considered as the standard, with observed response rates of 80–85% and approximately 25% of patients obtaining a complete response

However, most patients experience disease relapse. Attempts to improve the outcome using different or more dose-intensive chemotherapy regimens or maintenance chemotherapy have not led to improved outcomes.

Chemotherapy for Small Cell

Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data

JCO May 10, 2012 vol. 30 no. 14 1692-1698

Radiation for Small Cell

• Adding radiation to chemotherapy will lower the risk of lung relapse by 25 to 30% and increase the survival by 5 to 7%• Radiation dose to the lung can be twice a day to 45Gy or daily to 60 – 70 Gy

Twice-Daily Compared with Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated Concurrently with Cisplatin and Etoposide

N Engl J Med 1999; 340:265-271

 total dose of thoracic radiotherapy was 45 Gy for each patient, 1.8 Gy daily in 25 treatments over a period of five weeks or Accelerated twice-daily thoracic radiotherapy involved the administration of 1.5 Gy in 30 treatments over a period of three weeks.

• Low dose prophylactic cranial irradiation (PCI) reduced the risk of brain mets from 58% to 33% and increased 2y survival from 15% to 21% and another study showed a decreased risk of brain mets from 49% down to 14% and improved 1 year survival from 13% up to 27%

• Brain dose of 24 to 30Gy

Benefits of PCI (prophylactic cranial irradiation) of extensive stage small cell in lowering the

risk of developing brain metastases

Small cell cancer may shrink so quickly, it may be necessary to adjust the radiation target

Daily CT images on Tomo will allow for the physician to adjust the radiation target if the cancer changes in size or position

Typical CT Changes for Small Cell after Chemoradiation

PET-CT Changes for Small Cell after Chemoradiation

Results with ChemoradiationStage Respons

eSurviva

lSurviva

l

Limited Stage

70 – 90% 14 to 20 months

40%/2y

Extensive

60 – 70% 9 to 11 months

< 5%/2y

Stage 2 Year 5 Year

I 41.1% 21.5%

II 34.4% 17.2%

III 23.4% 9.5%

IV 5.9% 1.6%

Observed Survival for Small Cell Lung Cancer

NCDB Data (cases diagnosed in 2003 – 2005)

0%10%20%30%40%50%60%70%80%90%

100%

0 1 2 3 4 5

Stage I

Stage II

Stage III

Stage IV

Observed Survival for Small Cell Lung Cancer

NCDB Data (cases diagnosed in 2003 – 2005)

Small Cell Lung CancerRobert Miller MD

www.aboutcancer.com